The loss or failure of an organ or tissue can have a severe impact on the health and well-being of the affected person or animal. To understand the role of a particular organ or tissue in the body, how it grows, and its response to different agents, studies are done on samples of organ or tissue which are maintained in culture. The term "tissue" is used hereafter to refer to both organs and tissues. A problem in tissue culture studies is maintaining viability of the sample in culture. Another problem is the difficulty of routinely being able to prepare sections of tissue of a defined size for culturing. A lack of uniformity of the size of tissue sections means that accurate comparisons of results cannot be made.
Tissue samples are usually embedded by fixing the tissue in formalin and then embedding in paraffin. Other fixatives that may be used to preserve tissue samples include mercuric chloride, picric acid, glutaraldehyde, Bouin's fluid, and Zenker's formalin (Helly's fluid). In addition to paraffin, plastic resins may be used for embedding the tissue samples. Disadvantages of these fixatives and embedding materials arise from trauma to the tissue, toxicity of the embedding material, and difficulty in obtaining sections of defined size, particularly of soft tissue.
Fibrinogen is mitogenic and stimulates cell growth and viability. A human fibrin foam prepared by lyophilization of a solution of human fibrinogen has been used to culture tumors by placing pieces of tumor on top of 10.times.10.times.3 millimeter semi-cubes of fibrin foam sitting in culture medium. Kalus, M. et al., Cancer 22:507-516 (1968); Kalus, M. et al., Arch. Path. 86:52-59 (1968). A disadvantage of this method is that only one side of the tissue sample is in contact with the fibrinogen, which minimizes the stimulatory effect of the fibrinogen. (All of the documents cited or otherwise referenced herein are incorporated herein in their entirety for all purposes.)
Fibrin glue, usually made from freeze-dried plasma fibrinogen/factor XIII concentrate and thrombin, has been used in surgical applications such as replacement of sutures in skin grafts, nerve and vessel anastomoses, and surgery of parenchymal tissues of liver, lung, or spleen. In Itay U.S. Pat. Nos. 4,904,259 and 5,053,050, bone and cartilage are repaired by implanting a proliferating chondrocyte cell structure having phenotypic capability embedded in a biological glue consisting of 10-30% serum containing growth factors, 100 to 150 mg/ml fibrinogen, 60 to 90 U/ml thrombin, 60 mM CaCl.sub.2, and 2,000 U/ml (KIU) aproprotein.
There is a continuing need for methods for embedding and culturing tissues that are non-toxic to the tissue, that allow improved sectioning of the tissue with less trauma to the tissue, and that allow better diffusion of tissue culture fluid to the sectioned tissue.